title: Reduction of plasma membrane glutamate transport potentiates insulin but not glucagon secretion in pancreatic islet cells.
abstract: Glutamate is generated during nutrient stimulation of pancreatic islets and has been proposed to act both as an intra- and extra-cellular messenger molecule. We demonstrate that glutamate is not co-secreted with the hormones from intact islets or purified α- and β-cells. Fractional glutamate release was 5-50 times higher than hormone secretion. Furthermore, various hormone secretagogues did not elicit glutamate efflux. Interestingly, epinephrine even decreased glutamate release while increasing glucagon secretion. Rather than being co-secreted with hormones, we show that glutamate is mainly released via plasma membrane excitatory amino acid transporters (EAAT) by uptake reversal. Transcripts for EAAT1, 2 and 3 were present in both rat α- and β-cells. Inhibition of EAATs by L-trans-pyrrolidine-2,4-dicarboxylate augmented intra-cellular glutamate and α-ketoglutarate contents and potentiated glucose-stimulated insulin secretion from islets and purified β-cells without affecting glucagon secretion from α-cells. In conclusion, intra-cellular glutamate-derived metabolite pools are linked to glucose-stimulated insulin but not glucagon secretion.
authors.affiliation: Department of Cell Physiology and Metabolism, University Medical Centre, Geneva, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Feldmann
authors.forename: Rafael Martin
authors.initials: RM
authors.lastname: del Rio
authors.forename: Asllan
authors.initials: A
authors.lastname: Gjinovci
authors.forename: Jorge
authors.initials: J
authors.lastname: Tamarit-Rodriguez
authors.forename: Claes B
authors.initials: CB
authors.lastname: Wollheim
authors.forename: Andreas
authors.initials: A
authors.lastname: Wiederkehr
mesh_terms: D000409:Alanine / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D050491:Glutamate Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D003998:Dicarboxylic Acids; D050491:Glutamate Plasma Membrane Transport Proteins; D007328:Insulin; D007656:Ketoglutaric Acids; D008293:Malates; D011759:Pyrrolidines; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C030298:malic acid; D005934:Glucagon; C083486:pyrrolidine-2,4-dicarboxylic acid; D005947:Glucose; D000409:Alanine; D004837:Epinephrine